The work in progress under this grant is directed at the study of myocardial metabolism under conditions of surgical stress during and after cardiac bypass. Studies are underway in evaluating the myocardial utilization of various substrates during the period of hypothermic cardiac preservation and in the immediate post perfusion rewarming period when the myocardium must take over circulatory demands. This study of myocardial metabolism has been developed experimentally in a myocardial pedicle system which enables complete control of arterial inflow and coronary venous outflow in a segment of the intact working left ventricle of a dog from which all collaterals have been excluded. Techniques have been developed for the study of substrate metabolism using 13C labeled glucose which permits tracing of the metabolic byproducts of glucose through the Krebs cycle or into ketone and fat metabolism. The regulation of glucose metabolism under conditions of hypothermic preservation and during rewarm reperfusion are being studied. The effects of various substrate mixtures in both these periods is being correlated with the degree of return of effective myocardial electrical activity in coherent transmural propagation as an indicator of myocardial arrhythmogenic potential. These techniques are designed so as to be applicable to human studies once the basic outlines of the metabolic and electrical interaction are clear from the experimental work. Thus, they involve the use of nonradioactive 13C labeled substrates which can be ascertained by mass spectrometric techniques in a 50 mg biopsy taken during cardiopulmonary bypass and electrical measurements which can be made with a very fine gauge ventricular transmural needle electrode containing multiple ECG sensor tips. Studies of human myocardial metabolism are planned in cardiac surgical patients undergoing cardiopulmonary bypass and the clinical effect of various substrate mixtures with and without K ion cardioplegia will be evaluated in the setting of intrinsic myocardial disease.